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Diss Factsheets

Administrative data

Description of key information

Acute toxicity oral

The acute oral LD50 in male Sprague-Dawley rats was calculated to be 2760.6 mg/kg of body weight; the oral LD50 in females was calculated to be 3160.8 mg/kg of body weight.

Acute toxicity inhalation

LCLO(4 hour) for n-butyl bromide as a vapour is in excess of 25.4 mg/l in air.

Acute dermal toxicity

LD0 of the test substance n-BUTYL BROMIDE was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
October 18, 1979 to November 2, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
No further information specified.
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
No further details specified in the study report.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Fifty (twenty-five/sex) albino rats (Sprague-Dawley) were received for the study from A.R.S. Sprague-Dawley, Madison, Winconsin. The initial body weights of the males ranged from 189 to 230 grams, and the body weights of the females ranged from 195 to 225 grams. The rats were uniquely identified by an ear tag and housed individually in elevated wire-mesh cages. Commercial rodant ration (Purina Rodent Laboratory Chow) and tap water were available ad libitum except where noted otherwise. Rats were used in this study because they have historically been used in safety evaluation studies and are required by appropriate regulatory agencies.
Upon receipt, the twenty-five rats of each sex were assigned to the groups by a table of random numbers. The rats were acclimated to laboratory conditions for approximately one week prior to initiation of treatment.
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Appropriate amounts of the test material were administered by oral gavage following an overnight fast.
Doses:
1000, 1957.9, 3872.6, 7620.8 and 15,000 mg/kg
No. of animals per sex per dose:
10 per dose group (5 male/5 female)
Control animals:
no
Details on study design:
Observations and Records
All of the rats were observed for mortality and signs and toxic and pharmacologic effects at one, two and four hours post-dose, and twice daily thereafter for fourteen consecutive days. Individual body weights were recorded prior to treatment, on Day 7 and at termination.

Sacrifice and Gross Pathology
At termination (Day 14), all surviving rats were sacrificed by carbon dioxide asphyxiation, necropsied, and observations recorded. Necropsies were also performed on those animals which died during the study.
Statistics:
The mortality data was analysed by the moving average method (Weil. 1952).
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 760.6 mg/kg bw
Based on:
test mat.
95% CL:
> 2 234.1 - < 3 411.1
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
3 160.8 mg/kg bw
Based on:
test mat.
95% CL:
> 2 411 - < 4 143.8
Mortality:
Dose Level (mg/kg) Mortality (%)
Male Female
1000 0 0
1967.9 0 0
3872.6 100 80
7620.8 100 100
15,000 100 100
Clinical signs:
other: Clinical observations consisted of depression, rough coat, tremors, slight depression, and red stain on eyes and/or nose, noted at all dose levels: soft feces, ataxia, laboured respiration, and urine stains, noted at the 2967.9, 3872.6, 7620.8 and 15,000
Gross pathology:
Gross pathology consisted of bright red discoloration of the lungs, and fluid in the thoratic cavity, urinary bladder (dark black), and stomach and intestine (clear yellow), as well as material in the stomach and intestine (dark red, greenish, oily black, compound-like).
Other findings:
No other findings detailed in the study report.

Male and Female Cumulative Mortality Dataa

Acute Oral Toxicity Study of 08287902 in Rats

Dosage Level

mg/kg

Time Post-Dose

Percent Mortality

Hours

Days

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Males

1000

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1967.9

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3872.6

0

0

0

3

5

5

5

5

5

5

5

5

5

5

5

5

5

100

7620.8

0

0

1

5

5

5

5

5

5

5

5

5

5

5

5

5

5

100

15,000

0

0

0

5

5

5

5

5

5

5

5

5

5

5

5

5

5

100

Females

1000

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1967.9

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3872.6

0

0

0

0

4

4

4

4

4

4

4

4

4

4

4

4

4

80

7620.8

0

0

1

4

5

5

5

5

5

5

5

5

5

5

5

5

5

100

15,000

0

0

0

5

5

5

5

5

5

5

5

5

5

5

5

5

5

100

aData based on five animal/sex/group.

 

KEY to Daily Clinical Observations

N = Normal; D = Depression; R = Rough Coat; B = Red Stain on Nose and/or Eyes; S = Slight Depression; T = Tremors; F = Soft Feces; A = Ataxia; L = Labored Respiration; O = Lacrimation; E = Salivation; U = Urine Stains; H = Hunching; P = Prostrate

 

Individual Daily Clinical Observations

Acute Oral Toxicity Study of 08287902 in Rats

1000 mg/kg

Animal Number

Time Post-Dose

Hours

Days

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Males

D66848

N

RD

DR

DR

DR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66849

N

DR

DR

DR

DR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66850

N

DR

DR

DR

DR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66851

N

DR

DR

SR

SR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66852

N

DRB

DRB

SR

SR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Females

D66853

N

DRT

DRT

SRB

SRB

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66854

N

DR

DR

SRB

SRB

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66855

SR

DRBT

TBDR

SRB

SRB

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66856

R

DRB

DRB

DR

DR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66857

R

DR

DR

SR

SR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

1967.9 mg/kg

Animal Number

Time Post-Dose

Hours

Days

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Males

D66868

S

S

DRA

DR

DR

R

R

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66869

SF

DRFLA

DRAFL

DROEL

DRSLO

RB

RB

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66870

SF

DRFLA

DRFLA

DR

DR

R

R

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66871

DRA

DRFLA

DRFLA

SR

SR

R

R

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66872

DA

DRA

DRATO

SR

SR

R

R

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Females

D66873

S

DRUA

DRUAO

DRBU

DRBU

SR

SR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66874

S

DRUA

DRUAOL

DRBU

DRBU

SR

SR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66875

S

DRA

DRAO

SU

SU

SR

SR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66876

SRF

DRUT

DRUFO

SBU

SBU

SR

SR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66877

SR

DRA

DROAU

DBU

DBU

SR

SR

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

3872.6 mg/kg

Animal Number

Time Post-Dose

Hours

Days

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Males

D66878

S

DRA

DRAOE

DHPLUB

DHPLUB

Found dead

D66879

DRAF

DRAF

DRAOUF

Found dead

D66880

DRF

DRAF

DROUFA

Found dead

D66881

DRF

DRAFB

DROU

FLE

DHPLUB

DHPLUB

Found dead

D66882

S

DRAT

DRAT

OUF

Found dead

Females

D66883

S

DRAFT

DRAT

OFU

DRPLU

DRPLU

Found dead

D66884

SF

DRAFT

DRAT

OFU

DRPLU

DRPLU

Found dead

D66885

S

DRAT

DRAT

OFU

DRPLU

DRPLU

Found dead

D66886

SRF

DRAF

DRAT

OFU

DHPUB

DPHUB

DHPUB

DHPUB

SRUPB

SRUPB

SRU

SRU

RU

RU

U

U

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

D66887

RF

DRAFT

DRAT

OFU

DHPUB

DHPUB

Found dead

7620.8 mg/kg

Animal Number

Time Post-Dose

Hours

Days

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Males

D66888

R

DR

PLEOR

Found dead

D66889

SRAF

DRFA

TB

Found dead

D66890

SR

SRFA

DRAFULT

Found dead

D66891

R

DREA

FT

PLEOR

Found dead

D66892

SR

DRAT

PLEOR

Found dead

Females

D66893

DRF

DRFUA

PROFUL

Found dead

D66894

FDRA

DRFU

AT

DRFUAT

DHPLUB

DHPLUB

Found dead

D66895

DRBA

DRAB

TU

Found dead

D66896

DRBA

DRAB

FT

PRLTOE

UF

Found dead

D66897

SRA

DRAB

FT

DRUFOTA

Found dead

15,000 mg/kg

Animal Number

Time Post-Dose

Hours

Days

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Males

D66858

R

DR

ATUDRBL

Found dead

D66859

R

DRB

ATUDRB

Found dead

D66860

DR

PRL

PRL

Found dead

D66861

RF

DRF

BUDRF

Found dead

D66862

R

DRU

ADRU

Found dead

Females

D66863

R

TUDRB

TUADRB

Found dead

D66864

R

UDRB

TUADRB

Found dead

D66865

SR

TUDRB

TRPLU

Found dead

D66866

R

TUDRB

TUADRB

Found dead

D66867

R

PLR

PLR

Found dead

 

Gross Pathology Summary

Acute Oral Toxicity Study of 07287902 in Rats

ORGAN DESCRIPTION

Dosage Level (mg/kg):

1000

1967.9

3872.6

7620.8

15,000

Number of Animals Examined

Number with No Gross Pathology

10

10

10

10

10

1

10

0

10

0

LUNGS

           Bright red

 

 

 

 

 

10

THORACIC CAVITY

           Contained Fluid

 

 

 

5

 

 

STOMACH

           Contained Dark Red Material

           Contained Greenish Material

           Contained Oily Black Material

           Contained Compound-Like Material

           Contained Clear Yellow Fluid

 

 

 

5

2

 

 

 

8

2

 

 

 

 

 

10

INTESTINE

           Contained Dark Red Material

           Contained Greenish Material

           Contained Oily Black Material

           Contained Compound-Like Material

           Contained Clear Yellow Fluid

 

 

 

5

2

 

 

 

8

2

 

 

 

 

 

10

URINARY BLADDER

           Contained Dark Black Fluid

 

 

 

 

2

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
08287902 was evaluated for acute oral toxicity in male and female rats. Based upon the findings of this study, the acute oral LD50 in males was calculated to be 2760.6 mg/kg of body weight with 95% confidence limits from 2234.1 to 3411.1 mg/kg of body weight; the oral LD50 in females was calculated to be 3160.8 mg/kg of body weight, with 95% confidence limits from 2411.0 to 4143.8 mg/kg of body weight.
Executive summary:

08287902 was evaluated for acute oral toxicity in male and female rats. Based upon the findings of this study, the acute oral LD50 in males was calculated to be 2760.6 mg/kg of body weight with 95% confidence limits from 2234.1 to 3411.1 mg/kg of body weight; the oral LD50 in females was calculated to be 3160.8 mg/kg of body weight, with 95% confidence limits from 2411.0 to 4143.8 mg/kg of body weight.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08/09/1993 to 22/09/1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
O.E.C.D. guideline No. 401, 24 February 1987.
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
No further details specified in the study report.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species, strain: rat, Sprague-Dawley ICO: OFA-SD (IOPS Caw).
Reason for choice: rodent species currently required by International Authorities for this type of study.
Breeder: Iffa Credo, 69210 L’Arbresle, France.
Number and sex: one group of 10 animals (5 males and 5 females).
Age/weight: on the day of treatment, the animals were approximately 6 weeks old and had a mean weight of 179 ± 6 g for the males and 152 ± 2 g for the females.
Acclimatisation: at least 5 days before commencement of the study.
Animal identification: the animals were identified individually using perforations or notches in the flap of the ear.

Environment
During the acclimatisation period and during the study, the maintenance conditions of the animal housing facility were as follows:
Temperature: 22 ± 3°C
Humidity: 50 ± 20%
Nyctohemeral period: 12 hrs/12 hrs
Ventilation: around 13 cycles/hour of filtered and non-recycled air.
The temperature and humidity were recorded continuously and the results retained. The accommodation conditions (temperature, humidity, nyctohemeral period and ventilation) were checked each month.
The animals were housed in polycarbonate cages (48 x 27 x 20 cm) fitted with a stainless steel lid. Each cage housed 4 to 7 animals of the same sex for the acclimatisation period and 5 rats of the same sex for the treatment period. Each cage contained sawdust litter made from wood that was screened and had the dust removed (SICSA 94142 Alfortville, France).
Bacteriological analysis of the litter and testing for main contaminants (pesticides, heavy metals) were carried out regularly.

Food and drink
All animals had access to food "Rats and mice maintenance reference A04 C" (U.A.R., 91360 Villemoisson-sur-Orge, France), presented in the form of standardised stoppers.
Each batch of food was analysed (composition and contaminants) by the supplier.
Drinking water, filtered through an F.G. Millipore (0.22 microns), was distributed amongst feeding bottles.
Bacteriological and chemical as well as main contaminants (pesticides, heavy metals and nitrosamines) analyses were carried out regularly.

The non-nutritional substances that may have been present in the food, drinking water or litter were at a level where they were not able to interfere in the good conduct of the study.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The product was administered untouched, taking into account the density of the product d = 1.27.
Doses:
2000 mg/kg
No. of animals per sex per dose:
10 animals (5 males and 5 females).
Control animals:
no
Details on study design:
Administration was carried out once, orally, using a tube with a stainless steel eccentric tip (diameter: 18 G.2", Perfektum: Poffer & Sons Inc., New Hyde Park, New York 11040, U.S.A.) mounted on a 1 ml glass syringe (graduations of 0.01 ml, Record: Carrieri, 75005 Paris, France).
The volume administered to each animal was adjusted to the body weight determined on the day of treatment.

CLINICAL EXAMINATIONS
Clinical signs
Observation of the animals was carried out frequently during the hours following administration of the product. It was carried out at least once a day for the 14 days afterwards to note reversible or irreversible clinical signs. The appearance or disappearance of clinical signs was recorded for each animal.

Mortality
The mortality check was carried out frequently just after administration of the product and at least twice a day for a minimum of 14 days of observation.

Body weight
The animals were weighed individually just before administration of the product, then on days 5, 8 and 15.
The weight development of the treated animals was compared to a reference curve drawn up at C.I.T from untreated animals of the same initial weight.

PATHOLOGY
Autopsy
On day 15, the animals were sacrificed using inhalation of an excess of CO2 and underwent a macroscopic examination.

Macroscopic examination
After opening the abdominal and chest cavities, a macroscopic examination of the main organs was carried out: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and other organs with abnormalities.
The macroscopic observations were recorded individually. The organs presenting macroscopic lesions were sampled and preserved in a formaldehyde buffer at 10%.

Microscopic examination
No microscopic examination was carried out.
Statistics:
Not specified.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was found during the observation period.
Clinical signs:
other: At 2000 mg/kg, signs of hypoactivity or sedation and piloerection were observed in the 4 hours following the treatment. No clinical sign was observed between days 2 and 15.
Gross pathology:
There was no proof of a visible abnormality in the macroscopic examination of the main organs of the animals sacrificed at the end of the study.
Other findings:
No further findings reported.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions, the LD 0 of the product n-BUTYL BROMIDE administered orally in rats is greater than or equal to 2000 mg/kg.
Executive summary:

At the request of the Sponser, the acute toxicity of the product n-BUTYL BROMIDE was assessed orally in rats in accordance with the O.E.C.D guidelines. (No. 401, 24 February 1987). The study was carried out in accordance with the Good Laboratory Practice regulations.

 

Methods

The product was administered orally to a group of 10 Sprague-Dawley rats (5 males and 5 females) on a liquid diet. Administration was carried out with the product untouched at a dosage of 2000 mg/kg, taking into account the density of the product d = 1.27.

 

The clinical signs, mortality and weight development of the animals was monitored for a period of 14 days after single-dose administration of the product.

 

An anatomical pathological examination was carried out on each of the animals that were sacrificed at the end of the study.

 

Results

At 2000 mg/kg, a significant reduction in the spontaneous activity and piloerection were observed in the four hours following the treatment. No clinical signs were noted at day 2.

 

Mortality was zero at a dose of 2000 mg/kg.

 

The weight development in males was slightly slowed between days 1 and 5. The weight development in females was normal.

The autopsy of the animals that were sacrificed at the end of the study did not show any macroscopic abnormality.

 

Conclusion

Under the experimental conditions, the LD 0 of the product n-BUTYL BROMIDE administered orally in rats is greater than or equal to 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 760.6 mg/kg bw
Quality of whole database:
K2

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 March to 10 April 1997 and 14 May to 6 June 1997.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
not specified
GLP compliance:
yes
Test type:
traditional method
Limit test:
no
Specific details on test material used for the study:
No further details specified on the study report.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Fifteen male and 15 female albino rats (Sprague-Dawley) were selected from two consignments of rats obtained from Charles River UK Ltd, Manston Road, Margate, Kent, England on 19 March 1997 (10 male and 10 female) and 14 May (5 male, 5 female). The rats were selected so that males and females would be between 8 weeks and 9 weeks old on the day of exposure. The weight ranges were 182 - 213 g for males and 170 - 187 g for females when placed on the study.
On arrival the rats were allocated to 1 of 3 groups, each of 5 males and 5 females and were identified individually by a number tattooed on the ears. The rats were housed by sex in groups of 5 and acclimatised to laboratory conditions for at least 5 days before the day of exposure.
The holding cages (size 35 cm x 53 cm x 25 cm height) were made of stainless steel sheet and wire mesh and were suspended on a movable rack. While in their cages all rats had free access to a measured excess amount of food (SDS RMI) and tap water. Food and water supplies were analysed routinely to determine the levels of chemical or microbiological contaminants. Room lighting was by artificial light between 8 am and 8 pm daily.
The rats remained in a holding room except for the 4-hour exposure period and an overnight post exposure period when the rats in the test groups were kept in a ventilated cabinet to allow dispersal of any residual test substance.
The temperature and relative humidity of the holding room air was monitored continuously using a Kent Clearspan thermohygrograph. The temperature of the holding area during the study generally remained within the range of 21 °C± 2°C and the relative humidity was normally within the range 55% ± 10%. On one occasion and for a period of less than I hour the temperature and relative humidity of the room air fell to 16.5°C and 37% repectively. The extremes of temperature and relative humidity were considered unlikely to have influenced the results of the study.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
clean air
Remark on MMAD/GSD:
Not specified
Details on inhalation exposure:
Atmosphere generator
The atmosphere generator, was designed to produce and maintain an atmosphere containing vapour by evaporation of the test substance from a fritted glass disc with a counter current of air. All parts of the generator in contact with the test substance were made of glass. The test substance was delivered to the generator at a constant flow rate from a syringe driven by a syringe pump and the air supplied to the generator was dried, filtered and oil free.

Exposure chambers
The snout-only exposure chambers were of cylindrical form (30 cm id, 45 cm height) and made of aluminium alloy. The chambers had an enclosed volume of approximately 30 litres. The rats were held for exposure in moulded polycarbonate tubes which were attached at evenly spaced ports in the cylindrical section of the chamber. The tubes were tapered at one end to allow the snout only to project into the chamber. The other end was closed by insertion of an expanded plastic bung. A push rod passed through the centre of the bung and was adjusted to maintain the position of a rat during exposure. The tubes were attached to the chamber at parts in the mid-section of the chamber.
The test atmosphere entered the chamber through a port at the top centre of the chamber and was extracted at the base centre below the level of the rats. Each chamber was installed in a large fume cupboard exhausting through an absolute filter.

PROCEDURE
A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 10 litres per minute measured at the generator outlet tube. An in-line flow meter was used to monitor air flow throughout the exposure.
A syringe filled with the test substance was fitted to the syringe pump and connected to the generator with PTFE tubing. A flow rate of 0.18 ml/minute (Group 2) or 0.22 ml/minute (Group 3) was selected for the exposure. These flow rates were expected to give a vapour concentration of approximately 20 mg/l and in excess of 20 mg/l respectively.
The rats to be exposed were placed into restraining tubes. The tubes were attached to the ports in the mid section of the chamber.
The syringe pump and air supply were switched on and the exposure timed for 4 hours, following a
7-minute equilibration period.
After 4 hours, the supply of test substance was discontinued and the exposure chamber was allowed to clear before the rats were removed for examination.
Following exposure, the rats were returned to the holding cages and food and water supplies were restored. The test rats were kept in a ventilated cabinet overnight and then returned to the holding room for the remainder of the observation period.
The control group was treated similarly but exposed to clean dried air only.
The control rats were returned to the holding room at the end of the exposure procedure.

CHAMBER AIR TEMPERATURE
The air temperature in the exposure chamber was measured with a thermometer and recorded at the start of exposure and then at 30-minute intervals during the 4-hour exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
18.0 mg/l or 25.4 mg/l of air.
No. of animals per sex per dose:
One control group and 2 test groups each of 5 male and 5 female rats.
Control animals:
yes
Details on study design:
OBSERVATIONS
Clinical signs
The rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period. The clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours and then at hourly intervals during the exposure. During the observation period, the clinical signs were recorded once in the morning and then as necessary following a later check for clinical signs.
Bodyweight
All rats were weighed daily from the day of delivery to the Huntingdon Life Sciences up to and including the day of exposure. During the observation period rats were weighed on Days 7 and 14.
Food and water consumption
The amount of food and water consumed by each cage of rats was measured daily from the day of arrival. The daily mean intakes of food and water for each rat were calculated from the recorded data.
TERMINAL STUDIES
At the end of the 14-day observation period, the rats were killed by intraperitoneal injection of pentobarbitone sodium and exsanguinated when clinically dead.
All rats were subjected to a detailed macroscopic examination. The lungs were infused with, and preserved in, buffered 10% formalin together with samples of the liver and kidneys and retained until the study completion date.
Statistics:
Not specified
Key result
Sex:
male/female
Dose descriptor:
LCLo
Effect level:
> 25.4 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no deaths following exposure to the vapour of n-butyl bromide at a concentration of 18.0 mg/l or 25.4 mg/l of air.
Clinical signs:
other: During the exposure During exposure, signs seen in rats exposed to n-butyl bromide at 18.0 mg/l or 25.4 mg/l were exaggerated respiratory movements and shallow breathing. In addition, irregular respiration was seen in rats exposed at 25.4 mg/l. During th
Body weight:
The rate of bodyweight gain for the test rats was similar to that of the control rats.
Gross pathology:
Minimal congestion of all lobes of the lung and a small dark focus on the left lung were seen in 1 male test rat at 18.0 mg/l. There were no other macroscopic abnormalities in any rat.
Other findings:
Food consumption
Food consumption for test rats was slightly reduced on the day following exposure ton-butyl bromide. Otherwise food consumption for test rats was similar to that of the controls.

Water consumption
Water consumption in test rats (except for females at 25.4 mg/l) was slightly reduced on the day following exposure to n-butyl bromide. Otherwise water consumption for test rats was similar to that of the control rats.

Concentration of n-butyl bromide

Chemical analysis

Group

Sample

Time taken

(h:min)

Amount in air

(mg/l)

Nominal concentration1

(mg/l)

2

1

2

3

4

5

0:30

1:00

2:00

3:00

3:50

15.3

17.2

17.5

19.8

20.3

 

Mean

sd

18.0

2.04

24.3

1Calculated from the weight of test substance dispersed and the total volume of air supplied to the exposure system

sd Standard deviation

 

Chemical analysis

Group

Sample

Time taken

(h:min)

Amount in air

(mg/l)

Nominal concentration1

(mg/l)

3

1

2

3

4

5

0:30

1:00

2:00

3:00

3:50

25.0

27.3

25.0

25.2

24.7

 

Mean

sd

25.4

1.05

26.1

1Calculated from the weight of test substance dispersed and the total volume of air supplied to the exposure system

sd Standard deviation

 

Clinical signs during exposure

Group

Signs

Number showing signs

Time in hours

0*

0.25

0.5

1.0

2.0

3.0

4.0

1M

(Control)

Normal appearance and behaviour

Fur soiled with excreta

5

5

5

 

5

 

5

 

5

 

5

1F

(Control)

Normal appearance and behaviour

Fur soiled with excreta

5

5

5

 

5

 

5

 

5

 

5

2M

(18.0 mg/l)

Normal appearance and behaviour

Fur soiled with excreta

Shallow respiration

Exaggerated respiratory movements

5

5

4

 

 

1

 

5

4

1

 

5

4

1

 

5

4

1

 

5

 

5

2F

(18.0 mg/l)

Normal appearance and behaviour

Fur soiled with excreta

Shallow respiration

Exaggerated respiratory movements

5

5

5

 

5

4

1

 

5

4

1

 

5

4

1

 

5

 

5

3M

(25.4 mg/l)

Normal appearance and behaviour

Fur soiled with excreta

Irregular respiration

Exaggerated respiratory movements

Shallow respiration

5

3

 

 

2

 

 

4

1

 

 

 

2

3

 

 

 

 

5

 

5

 

5

 

5

 

5

3F

(25.4 mg/l)

Normal appearance and behaviour

Fur soiled with excreta

Irregular respiration

Exaggerated respiratory movements

Shallow respiration

5

5

 

 

5

 

 

 

 

5

 

 

 

 

5

 

5

 

5

 

5

 

5

*Clinical signs recorded during the 7-minute equilibration period

 

Clinical signs during observation period

Group

Signs

Number showing sign

Day of observation period

0hr*

1hr*

2hr*

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1M

(Control)

Normal appearance and behaviour

Fur soiled with excreta

 

5

 

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

1F

(Control)

Normal appearance and behaviour

Fur soiled with excreta

 

5

 

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

2M

(18.0 mg/l)

Normal appearance and behaviour

Fur soiled with excreta

Staggering

Wet fur around the snout and/or jaws

Peripheral vasodilation

Exaggerate respiratory movements

Matted fur

Brown staining around snout and/or jaws

 

5

5

5

5

4

 

5

 

4

3

5

 

1

1

1

1

1

5

1

3

 

 

 

 

1

 

2

5

5

5

5

5

5

5

5

5

5

5

5

5

2F

(18.0 mg/l)

Normal appearance and behaviour

Fur soiled with excreta

Staggering

Wet fur around the snout and jaws

Peripheral vasodilation

Exaggerated respiratory movements

Clear secretion from the eyes

Matted fur

Staining around the uro-genital region

Brown staining on the head

 

5

5

5

5

5

2

 

5

 

5

4

5

 

4

 

 

1

 

 

1

 

 

 

 

1

 

 

 

5

3

4

 

 

 

 

 

 

 

 

1

4

 

 

 

 

 

 

 

 

1

5

5

5

5

5

5

5

5

5

5

5

3M

(25.4 mg/l)

Normal appearance and behaviour

Fur soiled with excreta

Whole body tremors

Staggering

Wet fur around the snout and/or jaws

Peripheral vasodilation

Clear discharge from the eyes

 

5

1

5

5

5

2

 

5

 

1

5

 

5

 

1

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

3F

(25.4 mg/l)

Normal appearance and behaviour

Fur soiled with excreta

Staggering

Wet fur around the snout and/or jaws

Peripheral vasodilation

Clear discharge from the eyes

Red discharge from the eyes

Lethargy

Whole body tremors

 

5

5

4

5

4

1

1

2

 

5

1

5

 

 

 

1

1

 

5

1

5

 

 

 

1

1

 

5

5

5

5

5

5

5

5

5

5

5

5

5

5

*Clinical signs recorded after exposure on the day of exposure

 

Individual and group mean bodyweights (g)

Group

Rat

Day of observation

-5

-4

-3

-2

-1

0

7

14

1M

(Control)

21

22

23

24

25

234

232

228

230

227

248

253

242

240

240

260

263

251

255

250

273

278

258

262

259

280

287

264

275

266

287

297

269

280

274

354

368

310

334

321

407

419

337

378

356

Mean

230

245

356

266

274

281

337

379

1F

(Control)

26

27

28

29

30

190

197

197

192

203

198

191

195

203

198

199

210

201

208

203

202

211

208

216

208

199

208

213

219

212

208

201

203

221

209

228

225

224

243

230

239

244

235

265

244

Mean

196

197

204

209

210

209

230

245

2M

(18.0 mg/l)

31

32

33

34

35

242

240

231

221

242

261

254

242

234

256

273

268

256

248

266

278

282

269

259

278

290

293

276

271

285

298

300

285

272

294

335

259

327

314

335

379

419

376

343

382

Mean

235

249

262

273

283

290

334

380

2F

(18.0 mg/l)

36

37

38

39

40

205

192

205

189

193

212

187

196

201

198

217

201

209

205

202

223

204

209

208

209

219

204

217

206

210

223

198

209

216

205

233

217

230

231

224

251

223

243

243

243

Mean

197

199

207

211

211

210

227

241

3M

(25.4 mg/l)

1

2

3

4

5

227

252

229

231

250

239

262

239

247

262

243

268

246

254

268

251

274

254

265

276

262

283

263

274

283

269

288

271

282

292

210

322

309

332

320

364

364

349

389

359

Mean

238

250

256

264

273

280

319

365

3F

(25.4 mg/l)

6

7

8

9

10

211

199

208

196

208

217

204

220

203

213

218

209

228

203

213

220

206

232

200

209

225

216

239

211

222

223

217

240

214

222

244

233

244

223

242

257

248

254

234

251

Mean

204

211

214

213

223

223

237

249

0 = Day of exposure

 

Group mean daily food consumption (g/rat)

Group

Days

Pre-exposure

Post-exposure

-5

-4

-3

-2

-1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1M (Control)

35

35

34

34

34

29

35

35

32

36

34

35

37

36

35

35

35

34

32

2M (18.0 mg/l)

35

37

36

35

36

22

32

34

35

35

35

36

37

36

37

36

37

36

37

3M (25.4 mg/l)

33

33

34

34

34

16

31

33

33

33

33

33

33

33

35

33

36

34

33

1F (Control)

21

24

22

22

22

22

28

24

21

25

24

23

25

24

26

24

22

24

22

2F (18.0 mg/l)

23

26

26

23

24

13

23

24

24

27

29

25

23

24

27

26

22

24

25

3F (25.4 mg/l)

25

25

22

26

25

15

23

24

25

23

23

25

24

21

24

26

25

23

22

 

Group mean daily water consumption (g/rat)

Group

Days

Pre-exposure

Post-exposure

-5

-4

-3

-2

-1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1M (Control)

36

34

35

35

35

34

36

35

33

36

33

34

36

33

36

37

35

34

33

2M (18.0 mg/l)

26

35

36

34

35

23

36

34

28

33

33

33

33

34

32

34

35

36

37

3M (25.4 mg/l)

34

33

34

35

34

21

34

35

33

34

36

34

33

34

35

32

35

33

32

1F (Control)

21

27

24

23

22

25

27

24

21

28

25

24

24

26

28

28

23

28

26

2F (18.0 mg/l)

32

30

28

25

32

17

26

31

23

32

32

33

33

33

34

37

28

34

34

3F (25.4 mg/l)

30

30

26

32

29

26

28

37

35

31

29

33

31

29

31

32

31

27

28

 

Macroscopic pathology

Group

Rat

Region/organ affected

Observation

1M

(Control)

21

22

23

24

25

 

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

1F

(Control)

26

27

28

29

30

 

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

2M

(18.0 mg/l)

31

32

33

34

35

 

 

 

 

Lungs

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

Minimal congestion all lobes

Small dark subpleural foci left lung

2F

(18.0 mg/l)

36

37

38

39

40

 

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

3M

(25.4 mg/l)

1

2

3

4

5

 

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

3F

(25.4 mg/l)

6

7

8

9

10

 

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

No abnormalities detected

 

Interpretation of results:
GHS criteria not met
Conclusions:
The LCLO (4 hour) for n-butyl bromide is in excess of 25.4 mg/l in air.
Executive summary:

Test substance

A colourless liquid identified as n-butyl bromide (Batch No. 5-254-1).

 

Test animals

Albino rats, (Sprague-Dawley). One control group and 2 test groups each of 5 male and 5 female rats.

 

Route of administration

By inhalation of a test atmosphere containing a vapour generated from the test substance.

 

Duration of exposure

4 hours continuous snout only exposure.

 

Observation period

14 days post exposure.

 

Results

Exposure levels and mortality

           Group Level                        Mortality

                       (mg/l)             M        F         Total

           1         control           0/5      0/5      0/10

           2         18.0 mg/l        0/5      0/5      0/10

           3         25.4 mg/l        0/5      0/5      0/10

 

Clinical signs

Clinical signs seen in rats during exposure to n-butyl bromide were exaggerated respiratory movements and shallow breathing. Irregular respiration was also noted in rats exposed at 25.4 mg/l.

 

Signs seen in the test rats during a 2 hour post-exposure observation period were staggering, wet fur around the snout and jaws and peripheral vasodilatation. Exaggerated respiratory movements and matted fur were seen in rats exposed at 18.0 mg/1. Lacrimation was observed in 2 female rats. A clear (lacrimation) or red secretion from the eyes was observed in the rats exposed at 25.4 mg/l. On Day 1 of observation, staining around the urogenital region and brown staining on the head were also noted in female rats exposed at 18.0 mg/l.

 

Additional signs noted in rats exposed at 25.4 mg/l were whole body tremors and lethargy.

 

Male and female test rats exposed at 18.0 mg/l were normal in appearance and behaviour by Days 2 and 4 of the observation period respectively. Males and females exposed at 25.4 mg/l were normal in appearance and behaviour by Days 1 and 2 of the observation period respectively.

 

Fur soiled with excreta was evident in all test and control rats during and immediately following exposure. The sign was attributed to the method of restraint.

 

Bodyweight

The rate of bodyweight gain for the test rats was similar to that of the control rats.

 

Food and water consumption

Food consumption for test rats was slightly reduced on the day following exposure to n-butyl bromide. Otherwise food consumption for test rats was similar to that of the controls.

Water consumption in test rats (except for females exposed at 25.4 mg/l) was slightly reduced on the day following exposure ton-butyl bromide. Otherwise water consumption for test rats was similar to that of the control rats.

 

Macroscopic pathology

Minimal congestion of all lobes of the lung and a small dark focus on the left lung were seen in 1 male test rat at 18.0 mg/l. There were no other macroscopic abnormalities in any rat.

 

CONCLUSION

The LCLO(4 hour) for n-butyl bromide as a vapour is in excess of 25.4 mg/l in air.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
traditional method
Limit test:
no
Specific details on test material used for the study:
n-Butyl Bromide
Lot No. 11254
Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals or test system and environmental conditions:
Strain: Charles River Rats
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Remark on MMAD/GSD:
Not applicable - tet substanfce is a liquid
Details on inhalation exposure:
The vapor was generated by bubbling a stream of clean, dry air (-40 °C dewpoint) through the undiluted test material in a gas washing bottle. The resulting air-vapor mixture was then introduced into the exposure chamber.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
28.50, 42.88 and 54.97 mg/l air
No. of animals per sex per dose:
10 animals per dose (5 male/5 female)
Control animals:
no
Details on study design:
Observation period: 14 days
Complete necropsies were done on all rats that lived through the experiment when the study was terminated at the end of the 14-day post-exposure observation period. Similar examinations were done, as quickly after death as possible, on all rats that died during the experiment.
Statistics:
Not specified
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
37.06 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Group No. Mortality
Male Female
I 1/5 1/5
II 3/5 3/5
III 5/5 5/5
Clinical signs:
other: Ptosis, Dyspnea & Lacrimation reported.
Body weight:
The average 2-week bodv weight gains for surviving animals were within the norrnal limits.
Gross pathology:
No gross tissue changes attributed to the effects of the test material were observed in any of the rats that lived through the experiment.
Slight to moderate hydrothorax was observed in all rats in test group T-II that died during the experiment (3 male and 3 female rats). Hydrothorax was considered a secondary effect of the test material. Gross tissue changes observed in rats that dies during the experiment (1 male and 1 female from treatment group T-1 and all male and female rats from treatment group T-III) were considered normal post-mortem alterations.
Other findings:
No further details specified in the study report.

Group No.

Total Number of Animals

Male/Female

Nominal Concentration

Mortality

Male – Female

Weight Gain

Male – Female

(grams)

I

II

III

5/5

5/5

5/5

28.50 mg/l air

42.88 mg/l air

54.97 mg/l air

1/5 – 1/5

3/5 – 3/5

5/5 – 5/5

44 – 46

87 – 35

N.A. – N.A.

 

Reactions and Mortality

Group

Reaction

Number of Animals Affected

Time of Onset After Start of Exposure (min)

Duration

I

Ptosis

Ptosis

Dyspnea

Dyspnea

Lacrimation

Lacrimation

Anesthesia

Anesthesia

Death

8

2

8

2

8

2

8

2

2

10

10

12

12

15

15

220

220

>8<18 hrs.

>8<18 hrs.

Until death

>8<18 hrs.

Until death

>8<18 hrs.

Until death

50 min.

Until death

-

II

Ptosis

Ptosis

Dyspnea

Dyspnea

Lacrimation

Lacrimation

Anesthesia

Anesthesia

Death

4

6

4

6

4

6

4

6

6

5

5

5

5

7

7

180

180

>8<18 hrs.

>8<18 hrs.

Until death

>8<18 hrs.

Until death

>8<18 hrs.

Until death

180 min.

Until death

-

III

Ptosis

Dyspnea

Lacrimation

Anesthesia

Death

Death

Death

10

10

10

10

3

3

4

5

5

7

120

150

200

>8<18 hrs.

Until death

Until death

Until death

Until death

-

-

-

 

Interpretation of results:
GHS criteria not met
Conclusions:
LC50 37.06 mg/l air
Executive summary:

Strain: Charles River Rats

Exposure Data: Vapor Whole body exposure – 4 hours in duration, 14 days observation period

 

No gross tissue changes attributed to the effects of the test material were observed in any of the rats that lived through the experiment.

Slight to moderate hydrothorax was observed in all rats in test group T-II that died during the experiment (3 male and 3 female rats). Hydrothorax was considered a secondary effect of the test material. Gross tissue changes observed in rats that dies during the experiment (1 male and 1 female from treatment group T-1 and all male and female rats from treatment group T-III) were considered normal post-mortem alterations.

 

LC50 37.06 mg/l air

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Value:
25 400 mg/m³ air
Quality of whole database:
K1

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
16.1.96 to 30.1.96
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
O.E.C.D. guideline No. 402, 24th February 1987
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
E.C. Directive No. 92/69/E.E.C., B3, 31st July 1992.
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
No further details specified in the study report.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals
Species, strain: rat, Sprague-Dawley ICO: OFA-SD (lOPS Caw).
Reason for this choice: rodent species commonly requested by the international regulations for this type of study.
Breeder: Iff a Credo, 69210 L' Arbresle, France.
Number and sex: one group of ten animals (five males and five females).
Age/weight: on the day of treatment, the animals were approximately eight weeks old, and had a mean body weight ± standard deviation of 270 ± 5 g for the males and 221 ± 2 g for the females.
Acclimatization: at least five days before the beginning of the study.
Identification of the animals: the animals were identified individually by earmarks or ear notches.

Environmental conditions
During the acclimatization period and during the main test, the conditions in the animal room were set as follows:
temperature: 21 ± 2°C
relative humidity: 30 to 70%
light/dark cycle: 12 h/12 h
ventilation: about 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were recorded continuously and records retained.
The housing conditions (temperature, relative humidity, light/dark cycle and ventilation) were checked regularly.
The animals were housed in polycarbonate cages.
During the acclimatization period each cage (48 cm x 27 cm x 20 cm) contained four to seven animals of the same sex.
During the treatment period, the animals were housed individually (35.5 cm x 23.5 cm x 19.3 cm). Each cage contained dust-free sawdust (SICSA, 94142 Alfortville, France).
Bacteriological analysis of the sawdust and detection of possible contaminants (pesticides, heavy metals) are performed periodically.

Food and water
All the animals had free access to A04 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France).
Each batch of food was analysed (composition and contaminants) by the supplier.
Drinking water filtered by a F.G. Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analysis of the water and diet and detection of possible contaminants (pesticides, heavy metals and nitrosamines) are performed periodically.
It was verified that no contaminants in the diet or water at levels likely to influence the outcome of the study were present.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
As the test substance was anticipated to be non-toxic at 2000 mg/kg, a limit test was performed by application of 2000 mg/kg of the test substance to one group of ten animals (five males and five females).

Preparation of the animals
On the day before treatment, the dorsal area (6 cm x 8 cm) of each animal was clipped using electric clippers. Only animals with healthy intact skin were used for the study.

Administration of the test substance
The test substance was applied in its original form at a dose volume of 2000 mg/kg. It was placed directly on an area of the skin representing approximately 10% (5 cm x 6 cm for the females and 5 cm x 7 cm for the males) of the body surface of the animals. This was calculated according to Meeh's formula. A hydrophilic gauze pad (Semes France, 54183 Heillecourt, France) was then applied to the skin. The test substance and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing (Laboratoires de Pansements et d'Hygiene, 21300 Chenove, France) and a restraining bandage (Laboratoires 3M Sante, 92245 Malakoff, France). This dressing prevented ingestion of the test substance by the animals.
No residual test substance was observed at removal of the dressing.
The dose applied to each animal was adjusted according to body weight determined on the day of treatment.
Duration of exposure:
24 hours
Doses:
single administration
No. of animals per sex per dose:
group of ten animals (five males and five females).
Control animals:
yes, concurrent no treatment
Details on study design:
CLINICAL EXAMINATIONS
The single administration was performed in the morning on day 1; it was followed by a 14-day observation period until day 15.

Clinical signs and mortality
The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day. Type, time of onset and duration of clinical signs and local cutaneous reactions were recorded for each animal individually.
The time of death was recorded individually, in terms of the number of hours or days after dosing.

Body weight
The animals were weighed individually just before administration of the test substance on day 1 and then on days 8 and 15.
The body weight gain of the treated animals was compared to a reference curve of C.I.T. control animals with the same initial body weight.

NECROPSY
On day 15, all animals were killed by CO., inhalation in excess and a macroscopic examination was performed. -
After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.
In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin.
No microscopic examination was performed.
Statistics:
Not specified.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the observation period.
Clinical signs:
other: No clinical signs and no cutaneous reactions were observed during the study.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Interpretation of results:
GHS criteria not met
Conclusions:
Under our experimental conditions, the dermal LD0 of the test substance n-BUTYL BROMIDE was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.
Executive summary:

At the request of Elf Atochem S.A., Paris-la-Defense, France, the acute dermal toxicity of the test substance n-BUTYL BROMIDE was evaluated in rats according to O.E.C.D. (No. 402, 24th February 1987) and E.C. (92/69/E.E.C., B3) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

 

Methods

The test substance was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females) at a dose of 2000 mg/kg taking into consideration that the density of the test substance was 1.27. The test site was then covered by a semi-occlusive dressing for 24 hours.

Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single administration of the test substance.

All animals were subjected to necropsy.

 

Results

No cutaneous reactions were observed.

The general behaviour and body weight gain of the animals were not affected by treatment with the test substance.

No death occurred at 2000 mg/kg.

No abnormalities were observed at necropsy.

 

Conclusion

Under our experimental conditions, the dermal LD0 of the test substance n-BUTYL BROMIDE was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 May 2002- 30 May 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Commission Directive
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
No further details specified in the study report.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: their weight were: at least 200 g.
- 5 days of acclimatisation before start of study.
-Free access of water and food (certified rat and mouse diet- code 5LF2)
- Housing: suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hr exposure period and in groups of five, by sex, for the reminder of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): at least 15 changes per hr.
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
Area of exposure:
- % coverage: ca. 10 %
- Type of wrap if used: surgical gauze pad applied to skin with a semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24-hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): N/A
- Constant volume or concentration used: yes
- For solids, paste formed: N/A

VEHICLE
N/A
Duration of exposure:
24 hours.
Doses:
2000 mg/kg bw.
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequent observations of clinical signs were made 1/2, 1, 2, and 4 hours after dosing. Thereafter, observations were made at least once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Statistics:
Not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality during the observation period.
Clinical signs:
other: There were no signs of systemic toxicity.
Gross pathology:
No abnormalities obderved.
Other findings:
N/A
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The 24 hours dermal LD50 for 1-bromobutane was found to be > 2000 mg/kg/bw in rats . Therefore, the substance does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 93/21/EEC for classification and
labelling og dangerous substances and preparations.
Executive summary:

In an acute dermal toxicity study, 5 male and 5 female 8-12 weeks Sprague Dawley rats weighing at least 200 g dosed with a limit dose of 2000 mg/kg bw. A gauze pad was applied and then held in place with a semi-occlusive dressing. No dose related changes occurred during the 14 day observation period.

The 24 hours dermal LD50 for 1-bromobutane was found to be > 2000 mg/kg/bw in rats. Therefore, does not meet the critera for classification.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
K1

Additional information

Acute toxicity oral

08287902 was evaluated for acute oral toxicity in male and female rats. Based upon the findings of this study, the acute oral LD50 in males was calculated to be 2760.6 mg/kg of body weight with 95% confidence limits from 2234.1 to 3411.1 mg/kg of body weight; the oral LD50 in females was calculated to be 3160.8 mg/kg of body weight, with 95% confidence limits from 2411.0 to 4143.8 mg/kg of body weight.

The acute toxicity of the product n-BUTYL BROMIDE was assessed orally in rats in accordance with the O.E.C.D guidelines. (No. 401, 24 February 1987). The study was carried out in accordance with the Good Laboratory Practice regulations.

The product was administered orally to a group of 10 Sprague-Dawley rats (5 males and 5 females) on a liquid diet. Administration was carried out with the product untouched at a dosage of 2000 mg/kg, taking into account the density of the product d = 1.27.

 

Results

At 2000 mg/kg, a significant reduction in the spontaneous activity and piloerection were observed in the four hours following the treatment. No clinical signs were noted at day 2.

Mortality was zero at a dose of 2000 mg/kg.

The weight development in males was slightly slowed between days 1 and 5. The weight development in females was normal. 

The autopsy of the animals that were sacrificed at the end of the study did not show any macroscopic abnormality.

Conclusion

Under the experimental conditions, the LD 0 of the product n-BUTYL BROMIDE administered orally in rats is greater than or equal to 2000 mg/kg.

Acute toxicity inhalation

Albino rats, (Sprague-Dawley). One control group and 2 test groups each of 5 male and 5 female rats.

By inhalation of a test atmosphere containing a vapour generated from the test substance.

4 hours continuous snout only exposure.

14 days post exposure.

 

Results

Exposure levels and mortality

Group             Level (mg/l)                Mortality

                                               M        F         Total

1                     Control           0/5      0/5      0/10

2                     18.0 mg/l        0/5      0/5      0/10

3                     25.4 mg/l        0/5      0/5      0/10

 

Clinical Signs

Clinical signs seen in rats during exposure to n-butyl bromide were exaggerated respiratory movements and shallow breathing. Irregular respiration was also noted in rats exposed at 25.4 mg/l.

Signs seen in the test rats during a 2 hour post-exposure observation period were staggering, wet fur around the snout and jaws and peripheral vasodilatation. Exaggerated respiratory movements and matted fur were seen in rats exposed at 18.0 mg/l. Lacrimation was observed in 2 female rats. A clear (lacrimation) or red secretion from the eyes was observed in the rats exposed at 25.4 mg/l. On Day 1 of observation, staining around the urogenital region and brown staining on the head were also noted in female rats exposed at 18.0 mg/l.

Additional signs noted in rats exposed at 25.4 mg/l were whole body tremors and lethargy.

Male and female test rats exposed at 18.0 mg/l were normal in appearance and behaviour by Days 2 and 4 of the observation period respectively. Males and females exposed at 25.4 mg/l were normal in appearance and behaviour by Days 1 and 2 of the observation period respectively.

Fur soiled with excreta was evident in all test and control rats during and immediately following exposure. The sign was attributed to the method of restraint.

The rate of bodyweight gain for the test rats was similar to that of the control rats.

Macroscopic pathology

Minimal congestion of all lobes of the lung and a small dark focus on the left lung were seen in 1 male test rat at 18.0 mg/l. There were no other macroscopic abnormalities in any rat.

 

CONCLUSION

The LCLO(4 hour) for n-butyl bromide as a vapour is in excess of 25.4 mg/l in air.

Acute dermal toxicity

The test substance was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females) at a dose of 2000 mg/kg taking into consideration that the density of the test substance was 1.27. The test site was then covered by a semi-occlusive dressing for 24 hours.

Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single administration of the test substance.

All animals were subjected to necropsy.

 

Results

No cutaneous reactions were observed.

The general behaviour and body weight gain of the animals were not affected by treatment with the test substance.

No death occurred at 2000 mg/kg.

No abnormalities were observed at necropsy.

 

Conclusion

Under our experimental conditions, the dermal LD0 of the test substance n-BUTYL BROMIDE was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.

Justification for classification or non-classification

Acute toxicity oral

The test substance does not meet the criteria under CLP, therefore is Not Classified.

Acute toxicity inhalation

The test substance does not meet the criteria under CLP, therefore is Not Classified.

Acute dermal toxicity

The test substance does not meet the critiera under CLP, therefore is Not Classified.